Bacterial Involvement in Oral Squamous Cell Carcinoma and Potentially Malignant Oral Disorders - Original Article - Open Access

Sep 23, 2026

This open access study clarifies how oral squamous cell carcinoma (OSCC) relates to potentially malignant oral diseases (OPMDs) and oral bacterial flora through metagenomic analysis. A cross-sectional cohort compares control participants with OPMDs, early OSCC, and advanced OSCC. Salivary samples undergo high-throughput sequencing of 16S rRNA gene amplicons to quantify microbiome composition and diversity. Advanced OSCC shows higher diversity and a distinct clustering pattern, with specific taxa elevated across stages. Results support salivary microbiome as a biomarker for OSCC development and progression.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusions

Oral Diseases ORIGINAL ARTICLE OPEN ACCESS Cancer and Potentially Malignant Disorders Bacterial Involvement in Oral Squamous Cell Carcinoma and Potentially Malignant Oral Disorders Atsumu Koketsu1 | Satoshi Fukase1 | Toru Tamahara2 | Tatsuru Saito1 | Akiko Ito1 | Yutaro Higashi1 | Tomonari Kajita1 | Tsuyoshi Kurobane1 | Masaaki Miyakoshi1 | Masahiro Iikubo3 | Kazuki Kumada2,4 | Bin Li2,4 | Muneaki Shimada2,4 | Ritsuko Shimizu2 | Tetsu Takahashi1,5 | Kensuke Yamauchi5 | Tsuyoshi Sugiura1 1Division of Oral and Maxillofacial Oncology and Surgical Sciences, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan | 2Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan | 3Division of Dental Informatics and Radiology, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan | 4Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai, Miyagi, Japan | 5Division of Oral and Maxillofacial Reconstructive Surgery, Department of Disease Management Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Miyagi, Japan Correspondence: Atsumu Koketsu ([kouketsu_atsumu@dent.tohoku.ac.jp](kouketsu_atsumu@dent.tohoku.ac.jp)) Received: 13 March 2025 | Revised: 26 August 2025 | Accepted: 29 September 2025 Funding: This work was supported by the JSPS KAKENHI Grant Numbers 22K17150 . Keywords: leukoplakia | microbiota | mouth neoplasms | oral cancer | oral lichen planus (OLP) | oral potentially malignant diseases (OPMDs) | squamous cell carcinoma of head and neck ABSTRACT Objective: To clarify the relationship between oral squamous cell carcinoma (OSCC), potentially malignant oral disease (OPMD), and bacterial flora using metagenomic analysis. Methods: This cross-sectional observational study included 50 patients in the control group and 77 patients with OPMDs, 41 with early OSCCs, and 20 with advanced OSCCs. Patient saliva samples were subjected to high-throughput sequencing of 16SrRNA gene amplicons to evaluate the composition and diversity of the oral microbiome. Results: No significant differences were observed in patient backgrounds, other than sex. Patients with advanced OSCCs had greater oral bacterial diversity than those with early OSCC or OPMD. The advanced OSCC group formed a distinct cluster separate from the other groups. Sixteen and 275 species were identified at the phylum and genus levels, respectively. Compared with the control group, Actinomycetia and Streptococcus were significantly elevated in the early OSCC and OPMD groups. Peptostreptococcus and Fusobacterium were significantly higher in the advanced OSCC group than in the control, OPMD, and early OSCC groups. Conclusions: The composition and diversity of oral microbiota may be associated with OPMD development and progression to OSCC. Consequently, the salivary microbiome may serve as a biomarker for oral cancer and help predict cancer progression. 1 | Introduction The risk factors associated with squamous cell carcinoma include tobacco, alcohol, and human papillomavirus (HPV) and epithelial papillomavirus infections (Johnson et al. 2020; WHO Classification of Tumours Editorial Board 2022). Among the various squamous cell carcinomas, oral squamous cell carcinoma (OSCC) may arise from a subset of oral potentially malignant oral diseases (OPMDs), which are clinical conditions associated with an increased risk of malignancy. Leukoplakia is the most common OPMD (World Health Organization 2024; WHO Classification of Tumours Editorial Board 2022) . Leukoplakia is defined as “a predominantly white plaque of questionable risk having excluded (other) known diseases or disorders that carry no increased risk for cancer,” as proposed by Warnakulasuriya et al. (2007, 2021). It is a clinical diagnosis of exclusion and cannot This is an open access article under the terms of the Creative Commons Attribution Lice

FAQs

What is the objective of the study?

To clarify the relationship between oral squamous cell carcinoma, potentially malignant oral disease, and oral bacterial flora using metagenomic analysis.

How were oral microbiota samples analyzed?

Patient saliva samples were analyzed using high-throughput sequencing of 16S rRNA gene amplicons to assess microbiome composition and diversity.

What differences were observed between early and advanced OSCC?

Advanced OSCC patients showed greater oral bacterial diversity and formed a distinct cluster separate from early OSCC and OPMD groups. Specific bacterial taxa also differed by disease stage.

Sep 23, 2026

Uploaded by MrHarris58